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DOXAZOSIN TABLETS 8MG

Active substance(s): DOXAZOSIN MESILATE / DOXAZOSIN MESILATE

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SUMMARY OF PRODUCT CHARACTERISTICS

1

NAME OF THE MEDICINAL PRODUCT
Doxazosin Tablets 8mg

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 8mg doxazosin (as mesilate). For excipients, see 6.1.

3

PHARMACEUTICAL FORM
Tablet. White to off-white biconvex uncoated tablet, scored with a division mark on both sides and embossed with DZS 8 on one side.

4
4.1

CLINICAL PARTICULARS
Therapeutic indications Doxazosin Tablets are indicated for management of hypertension, as the sole agent, or in combination with a thiazide diuretic, ACE inhibitor, beta-blocker or calcium antagonist, and for the treatment of urinary outflow obstruction and symptoms associated with benign prostatic hyperplasia (BPH).

4.2

Posology and method of administration Adults and the elderly: Hypertension: Doxazosin Tablets should be taken once a day.

Initial dosage 1mg once daily preferably at bedtime. This may be increased after 1-2 weeks to 2mg daily, and thereafter to 4mg daily, if necessary. The majority of patients who respond to doxazosin will do so at a dose of 4mg or less. Dosage can be further increased if necessary to 8mg or to a maximum daily dose of 16mg. Benign prostatic hyperplasia: Initial dosage 1mg once daily preferably at bedtime. Depending on the patients response, the daily dosage may be increased to 2mg, and thereafter 4mg, up to a maximum dosage of 8mg per day. The recommended titration interval is 1-2 weeks and the usual recommended dose is 2-4mg daily.

Children: Doxazosin Tablets are not recommended for children. Oral administration.

4.3

Contraindications Doxazosin Tablets are contra-indicated in patients with known hypersensitivity to quinazolines patients with a history of orthostatic hypotension patients with benign prostatic hyperplasia and concomitant congestion of the upper urinary tract, chronic urinary tract infection or bladder stones



during lactation (see section 4.6 Pregnancy and Lactation)

Doxazosin is contraindicated as monotherapy in patients with either overflow bladder or anuria with or without progressive renal insufficiency.

4.4

Special warnings and precautions for use Initiation of Therapy: in relation to the alpha-blocking properties of doxazosin, patients may experience postural hypotension evidenced by dizziness and

weakness, or rarely loss of consciousness (syncope), particularly with the commencement of therapy. Therefore, it is prudent medical practice to monitor blood pressure on initiation of therapy to minimise the potential for postural effects. The patient should be cautioned to avoid situations where injury could result should dizziness or weakness occur during the initiation of doxazosin therapy. Use in patients with Acute Cardiac Conditions: as with any other vasodilatory anti-hypertensive agent it is prudent medical practice to advise caution when administering doxazosin to patients with the following acute cardiac conditions: pulmonary oedema due to aortic or mitral stenosis heart failure at high output right-sided heart failure due to pulmonary embolism or pericardial effusion left ventricular heart failure with low filling pressure. Use in Hepatically Impaired Patients: as with any drug wholly metabolised by the liver, doxazosin should be administered with particular caution to patients with evidence of impaired hepatic function. Since there is no clinical experiences in patients with severe hepatic impairment, use in these patients is not recommended. Use with PDE-5 inhibitors: concomitant administration of phosphodiesterase5-inhibitors (e.g. sildenafil, tadalafil and vardenafil) and doxazosin may lead to symptomatic hypotension in some patients. In order to minimise the risk for developing postural hypotension the patient should be stable on the alphablocker therapy before initiating use of phosphodiesterase-5-inhibitors. Use in patients undergoing cataract surgery: the Intraoperative Floppy Iris Syndrome (IFIS, a variant of small pupil syndrome) has been observed during cataract surgery in some patients on or previously treated with tamsulosin. Isolated reports have also been received with other alpha-1 blockers and the possibility of a class effect cannot be excluded. As IFIS may lead to increased procedural complications during the cataract operation, current or past use of alpha-1 blockers should be made known to the ophthalmic surgeon in advance of surgery. Excipients: Doxazosin Tablets 8mg contain lactose. Therefore, they should not be administered to persons with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption. Following the initial dose, postural hypotension may occur which may be severe and lead to collapse. This reaction can be avoided by starting treatment with a low dose at bedtime.

4.5

Interaction with other medicinal products and other forms of interaction Doxazosin is able to increase the antihypertensive effect of other antihypertensive agents. Although doxazosin binds well to plasma proteins it has not been found to have any effect on the protein binding of digoxin, phenytoin, warfarin or indomethacin in vitro, however the potential for such interaction should be borne in mind. No adverse interactions have been observed with frusemide, thiazide diuretics, beta-blockers, non steroidal anti-inflammatory drugs, anticoagulants, antibiotics, oral hypoglycaemics or uricosuric drugs. Care should be taken when doxazosin is co-administered with anti-depressants known to block alpha-1-adrenoceptors.

Concomitant use of phosphodiesterase-5-inhibitors (e.g. sildenafil, tadalafil and vardenafil) and doxazosin may lead to symptomatic hypotension in some patients (see section 4.4). In an open-label, randomised, placebo-controlled trial in 22 healthy male volunteers, the administration of a single 1mg dose of doxazosin on day 1 of a four-day regiment of oral cimetidine (400mg twice daily) resulted in a 10% increase in mean AUC of doxazosin and no statistically significant changes in mean Cmax and mean half-life of doxazosin. The 10% increase in the mean AUC for doxazosin with cimetidine is within intersubject variation (27%) of the mean AUC of doxazosin with placebo.

4.6

Fertility, pregnancy and lactation Doxazosin Tablets are not recommended during pregnancy, unless in the opinion of the physician the potential benefit to the mother outweighs the potential risk to the child. Teratogenic effects were not seen during animal testing, but reduced foetal survival was observed with very high doses (approximately 300 times the maximum recommended human dose). There have been no studies in pregnant women and therefore safety of use during pregnancy has not been established. Doxazosin Tablets are contra-indicated during lactation. Animal studies have shown that doxazosin accumulates in breast milk. The clinical safety of Doxazosin Tablets during lactation has not been established, consequently Doxazosin Tablets are contra-indicated in nursing mothers.

4.7

Effects on ability to drive and use machines The patients ability to drive and use machines may be impaired, particularly when treatment with doxazosin is first started.

4.8

Undesirable effects Frequencies used are as follows: very common 1/10, common 1/100 and < 1/10, uncommon 1/1,000 and < 1/100, rare 1/10,000 and <1/1,000, very rare <1/10,000.

MedDRA System Organ Class Infections and infestations Blood and lymphatic system disorders Immune system disorders Metabolism and nutrition disorders Psychiatric disorders

Frequency

Undesirable Effects

Common

Respiratory tract infection, urinary tract infection Leukopenia, thrombocytopenia

Very rare

Uncommon

Allergic drug reaction

Common Uncommon Common Uncommon

Anorexia Gout, increased appetite Anxiety, insomnia, nervousness Agitation, depression Dizziness, headache Dizziness postural, paraesthesia, somnolence

Nervous system disorders

Very common Common

Uncommon

Cerebrovascular accident, hypoaesthesia, syncope, tremor

Eye disorders

Very rare Unknown

Blurred vision Intraoperative Floppy Iris Syndrome (see section 4.4) Vertigo

Ear and labyrinth

Common

disorders Cardiac disorders

Uncommon Common Uncommon Very rare

Tinnitus Palpitations, tachycardia Angina pectoris, myocardial infarction, cardiac arrhythmias, Bradycardia Hypotension, postural hypotension Hot flushes Bronchitis, cough, dyspnoea, rhinitis Epistaxis, cough Bronchospasm aggravated Abdominal pain, dyspepsia, dry mouth, nausea, diarrhoea Constipation, flatulence, vomiting, gastroenteritis

Vascular disorders

Common Uncommon

Respiratory, thoracic and mediastinal disorders Gastrointestinal disorders

Common Uncommon Very rare Common Uncommon

Unknown Hepatobiliary disorders Uncommon Very rare Skin and subcutaneous Common tissue disorders Uncommon Very rare Musculoskeletal and connective tissue disorders Renal and urinary disorders Common Uncommon Very rare Common Uncommon

Taste disturbances Abnormal liver function tests Cholestasis, hepatitis, jaundice Pruritus Skin rash, alopecia, purpura Urticaria Back pain, myalgia Arthralgia, muscle cramps, muscle weakness Cystitis, urinary incontinence Dysuria, micturition frequency increased, haematuria, polyuria Increased diuresis, micturition disorder, nocturia

Reproductive system and breast disorders

Uncommon Very rare Unknown

Impotence Gynecomastia, priapism Retrograde ejaculation Asthenia, chest pain, influenza-like s ymptoms, peripheral oedema, fatigue,

General disorders and Common administration site conditions

malaise Uncommon Investigations Uncommon Pain, facial oedema Weight increase

4.9

Overdose In the event of overdose, supportive measures may be appropriate. If overdosage leads to hypotension, the patients should be placed in a supine, head down position straight away. As doxazosin is highly protein bound, dialysis is not recommended. If this measure is inadequate, shock should first be treated with volume expanders. If necessary, vasopressor should then be used. Renal function should be monitored and supported as needed

5
5.1

PHARMACOLOGICAL PROPERTIES
Pharmacodynamic properties Doxazosin is a potent and selective post-junctional alpha-1-adrenoceptor agonist which acts to lower systemic blood pressure. In benign prostatic hyperplasia, doxazosin improves symptoms by selective blockade of alphaadrenoceptors located in the prostatic muscular stroma, capsule and bladder neck. In addition to the antihypertensive effect of doxazosin, a modest reduction in plasma total cholesterol, LDL-cholesterol and triglyceride concentrations has been observed in long-term studies. Doxazosin may therefore be of particular benefit to hypertensive patients with concomitant hyperlipidaemia.

Doxazosin is considered to be suitable for use in patients with co-existent diabetes, gout and insulin resistance as it has been shown to be free of adverse metabolic effects.

5.2

Pharmacokinetic properties Following oral administration, doxazosin is well absorbed and binds to plasma proteins (98%) with approximately 60-65% of the dose being available. Peak plasma levels occur approximately 2 hours after an oral dose. Plasma concentrations of metabolites remain low. Plasma elimination is biphasic; the mean plasma elimination half-life being approximately 22 hours. Doxazosin is extensively metabolised in the liver, and excreted in the faeces as metabolites and a low quantity of unchanged drug.

5.3

Preclinical safety data There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

6
6.1

PHARMACEUTICAL PARTICULARS
List of excipients Microcrystalline cellulose Sodium lauryl sulphate Lactose monohydrate Sodium starch glycollate Colloidal silicon dioxide Magnesium stearate.

6.2

Incompatibilities Not applicable

6.3

Shelf life 36 months.

6.4

Special precautions for storage Store in the original package. Do not store above 25C.

6.5

Nature and contents of container PVC/PVdC/aluminium blister strips packed in an outer carton, Amber glass type III jars with HDPE child resistant closures, or HDPE tablet containers with polypropylene child resistant closures. Pack sizes: 28, 30 or 56.

6.6

Special precautions for disposal No special requirements.

7

MARKETING AUTHORISATION HOLDER
Ennogen Pharma Limited Unit G4 Riverside Industrial Estate Riverside Way Dartford DA1 5BS U.K

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MARKETING AUTHORISATION NUMBER(S)
PL 40147/0030

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DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
20/07/2012

10

DATE OF REVISION OF THE TEXT
20/07/2012

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Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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